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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02329847




Registration number
NCT02329847
Ethics application status
Date submitted
30/12/2014
Date registered
1/01/2015
Date last updated
15/06/2023

Titles & IDs
Public title
A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Participants With Hematologic Malignancies
Scientific title
A Phase 1/2a Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Subjects With Hematologic Malignancies
Secondary ID [1] 0 0
PCI-32765LYM1002
Secondary ID [2] 0 0
CR106681
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematologic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Nivolumab

Experimental: Cohort A1 - Participants will receive ibrutinib 420 milligram (mg) capsule orally once daily and nivolumab intravenously as 3 milligram/kilogram (mg/kg) every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort A2 - Participants will receive ibrutinib 560 mg capsule orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B1 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B2 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B3 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B4 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.


Treatment: Drugs: Ibrutinib
Participants will receive oral capsule of ibrutinib once daily as either 420 mg or 560 mg or at recommended Phase 2 dose in any of the cohort.

Treatment: Drugs: Nivolumab
Participants will receive nivolumab intravenously as 3 mg/kg on Day 1 every cycle of 14 days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) as Assessed International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008: Disease Cohort
Timepoint [1] 0 0
Up to 6 years 11 months
Primary outcome [2] 0 0
Overall Response Rate (ORR) as Assessed Non-Hodgkin Lymphoma (NHL), Cheson 2014: Disease Cohort
Timepoint [2] 0 0
Up to 6 years 11 months
Primary outcome [3] 0 0
Percentage of Participants With Treatment-emergent Adverse Event (TEAEs): Study Cohort
Timepoint [3] 0 0
Up to 6 years 10 months
Secondary outcome [1] 0 0
Duration of Response (DoR): Study Cohort
Timepoint [1] 0 0
Up to 6 years 11 months
Secondary outcome [2] 0 0
Duration of Stable Disease or Better: Study Cohort
Timepoint [2] 0 0
Up to 6 years and 11 months
Secondary outcome [3] 0 0
Progression-free Survival (PFS): Study Cohort
Timepoint [3] 0 0
Up to 6 years 11 months
Secondary outcome [4] 0 0
Overall Survival (OS): Study Cohort
Timepoint [4] 0 0
Up to 6 years 11 months
Secondary outcome [5] 0 0
Percentage of Participants With Lymphoma-related Symptoms: Study Cohort
Timepoint [5] 0 0
Up to 6 years 11 months

Eligibility
Key inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2
* Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil count (ANC) greater than equal to (>=) 1.5* 10^9cells/litre (L); 2) Platelets >=75 x 109cells/L without transfusion support within 7 days prior to test; 3) Hemoglobin >= 8 gram/deciliter (g/dL) without transfusion support within 7 days prior to test 4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than equal to (<=) 2.5 * upper limit of normal (ULN) 5) Total bilirubin less than (<) 2 milligram/deciliter (mg/dL) 6) Creatinine determined by serum creatinine levels <=1.5 * ULN or a calculated creatinine clearance of >= 50 mL/min/1.73 m^2
* Histologically confirmed B-cell non-Hodgkin lymphoma (B-NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
* Relapsed refractory disease after at least 1 but not more than 4 lines of previous systemic therapy
* Measurable disease (NHL: At least 1 measurable site of disease [>1.5 centimeter [cm] in the long axis regardless of short axis measurement or >1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions])
* Cohort B-1: SLL/CLL: 1) Deletion of short arm of chromosome 17 or 11 q based on institutional assessment 2) Relapsed/refractory after at least 1 prior systemic therapy 3) Active disease based in IWCLL criteria
* Cohort B-2: 1) B- cell follicular lymphoma Grade 1, 2, or 3a (WHO criteria) 2) Relapsed/refractory disease >= 2 lines separated by Progression, prior treatment (or not eligible for receiving) CD20 antibody 3) Measurable disease (IWG -Lugano 2014)
* Cohort B-3: 1) Histologically-confirmed DLBCL 2) Prior standard rituximab + anthracyclin containing regimen, received or not eligible or considered candidate of HD-ASCT 3) Measurable disease (IWG -Lugano 2014)
* Cohort B-4: 1) Histologically-confirmed Richter syndrome defined as transformation of CLL or SLL into an aggressive lymphoma 2) Previously treated with at least one line of standard, systemic chemotherapy or not eligible for standard therapy 3) At least 1 measurable site of disease based on the Revised Response Criteria for Malignant Lymphoma
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior therapy or surgery (3 to 10 weeks depending type)
* Prior BTK inhibitor or anti PD1, anti PDL1, anti PD-L2 and anti-CD137, anti-cytotoxic T-lymphocyte associated antigen (CTLA-4) antibody
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, or congenital long QT syndrome, or QT interval corrected for heart rate, using Fridericia formula (QTcF) at Screening greater than (>) 470 milliseconds (ms)
* History of stroke or intracranial hemorrhage within 6 months prior to the first dose of ibrutinib
* Requires treatment with anticoagulation with warfarin or equivalent vitamin K antagonists
* Requires treatment with strong cytochrome P450 3A (CYP3A) inhibitors
* Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/03/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/02/2022
Sample size
Target
Accrual to date
Final
144
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Bedford Park
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
Israel
State/province [2] 0 0
Haifa
Country [3] 0 0
Israel
State/province [3] 0 0
Jeursalem
Country [4] 0 0
Israel
State/province [4] 0 0
Ramat Gan
Country [5] 0 0
Israel
State/province [5] 0 0
Tel Aviv
Country [6] 0 0
Poland
State/province [6] 0 0
Chorzow
Country [7] 0 0
Poland
State/province [7] 0 0
Gdansk
Country [8] 0 0
Poland
State/province [8] 0 0
Krakow
Country [9] 0 0
Poland
State/province [9] 0 0
Wroclaw
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid
Country [12] 0 0
Spain
State/province [12] 0 0
Salamanca
Country [13] 0 0
Turkey
State/province [13] 0 0
Ankara
Country [14] 0 0
Turkey
State/province [14] 0 0
Istanbul
Country [15] 0 0
Turkey
State/province [15] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and to establish the recommended phase 2 dose (RP2D) for the combination of ibrutinib and nivolumab in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular cell lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Once the dose is optimized, the combination will be assessed for Pharmacokinetics, Pharmacodynamics, and preliminary efficacy, further safety in participants with CLL/SLL, FL or DLBCL and in participants with Richter syndrome.
Trial website
https://clinicaltrials.gov/study/NCT02329847
Trial related presentations / publications
Bruscaggin A, di Bergamo LT, Spina V, Hodkinson B, Forestieri G, Bonfiglio F, Condoluci A, Wu W, Pirosa MC, Faderl MR, Koch R, Schaffer M, Alvarez JD, Fourneau N, Gerber B, Stussi G, Zucca E, Balasubramanian S, Rossi D. Circulating tumor DNA for comprehensive noninvasive monitoring of lymphoma treated with ibrutinib plus nivolumab. Blood Adv. 2021 Nov 23;5(22):4674-4685. doi: 10.1182/bloodadvances.2021004528. Erratum In: Blood Adv. 2023 Jan 10;7(1):159-161. doi: 10.1182/bloodadvances.2022007909.
Younes A, Brody J, Carpio C, Lopez-Guillermo A, Ben-Yehuda D, Ferhanoglu B, Nagler A, Ozcan M, Avivi I, Bosch F, Caballero Barrigon MD, Hellmann A, Kuss B, Ma DDF, Demirkan F, Yagci M, Horowitz NA, Marlton P, Cordoba R, Wrobel T, Buglio D, Streit M, Hodkinson BP, Schaffer M, Alvarez J, Ceulemans R, Balasubramanian S, de Jong J, Wang SS, Fourneau N, Jurczak W. Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Lancet Haematol. 2019 Feb;6(2):e67-e78. doi: 10.1016/S2352-3026(18)30217-5. Epub 2019 Jan 11.
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02329847